Project Background
A biotechnology research team was investigating a MYC-driven tumor biology program and wanted to determine whether an oligonucleotide-guided degradation strategy could reduce MYC protein levels more effectively than transcriptional interference alone. The client had selected several MYC-associated E-box DNA motifs but lacked a clear strategy for choosing oligonucleotide length, conjugation site, E3 ligand, linker chemistry, and cellular assay conditions.
Our Support
BOC Sciences first reviewed the target biology, MYC/MAX DNA-binding behavior, available cell models, and antibody-based detection conditions. We then designed 26 oligoTRAFTAC candidates using three E-box-derived oligonucleotide variants, two terminal conjugation positions, VHL- and CRBN-recruiting ligand options, and PEG or semi-rigid heterocyclic linkers ranging from 8 to 18 atoms. Initial screening at 6 h, 16 h, and 24 h showed that short linkers retained binding-associated activity but produced limited MYC reduction, suggesting insufficient E3 proximity. A second optimization round prioritized a mid-length PEG-heterocycle hybrid linker and improved cellular treatment conditions. The best candidate produced reproducible MYC reduction with Dmax above 60% in the optimized cell model, while scrambled-sequence controls showed substantially weaker protein loss, supporting sequence-dependent target engagement.
Client Testimonial
BOC Sciences helped us transform a high-risk transcription factor concept into a structured TRAFTAC workflow. Their ability to connect oligonucleotide sequence design, E3 ligand selection, linker optimization, and degradation assay interpretation gave us a much clearer path for MYC-targeted degradation research.
Project Background
A discovery group was evaluating brachyury as a transcription factor target in a chordoma-related research program. The client had identified a candidate DNA motif but observed inconsistent target reduction in early oligonucleotide conjugate experiments. They needed support to determine whether the issue came from motif selection, conjugation chemistry, cellular delivery, or weak proteasome-dependent degradation.
Our Support
We began by comparing reported brachyury-binding sequence preferences and generated a small motif panel containing six sequence variants with matched scrambled controls. Binding analysis identified two motifs with stronger protein engagement, which were advanced into TRAFTAC conjugate synthesis. We prepared 20 candidates using a VHL-recruiting ligand, two linker attachment sites, and alkyl, PEG, and rigid linker families. The first degradation screen showed that highly flexible PEG linkers improved cellular response but also increased nonspecific effects at higher concentrations. We then introduced a shorter semi-rigid linker and optimized the treatment window to 16 h, followed by proteasome-dependence and ubiquitination validation. The optimized construct produced clearer brachyury degradation across two cell models and gave the client a defined design template for further analog expansion.
Client Testimonial
The BOC Sciences team did not simply synthesize conjugates. They helped us diagnose why our early TRAFTAC designs were inconsistent and established a practical optimization path supported by motif controls, degradation kinetics, and mechanism-focused validation.
Addresses Difficult Transcription Factors
